Dupilumab does not affect correlates of vaccine-induced immunity: A randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis - 13/12/18
, Eric L. Simpson, MD, MCR b, Stephen K. Tyring, MD, PhD c, Lisa A. Purcell, PhD d, Brad Shumel, MD d, Christopher D. Petro, PhD d, Bolanle Akinlade, MD d, Abhijit Gadkari, PhD d, Laurent Eckert, PhD e, Neil M.H. Graham, MBBS, MD, MPH d, Gianluca Pirozzi, MD, PhD f, Robert Evans, PharmD gAbstract |
Background |
The impact of dupilumab, an anti–interleukin (IL) 4 receptor α antibody that inhibits IL-4 and IL-13 signaling, on vaccine responses of patients with atopic dermatitis (AD) is unknown.
Objectives |
To assess T-cell–dependent and T-cell–independent humoral immune responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety.
Methods |
In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at week 16.
Results |
In total, 178 patients completed the study. Similar positive immune responses (≥4-fold increase in antibody titer, or an antibody titer of ≥8) were achieved in the dupilumab and placebo groups to tetanus (83.3% and 83.7%, respectively) and meningococcal polysaccharide (86.7% and 87.0%, respectively). Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap-IgE seronegative at week 32 (62.2% dupilumab and 34.8% placebo). Dupilumab improved key AD efficacy endpoints (P < .001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo.
Limitation |
Patients’ prior vaccination status was not available before enrollment.
Conclusion |
Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : atopic dermatitis, dupilumab, IgE, meningococcal polysaccharide, tetanus toxoid, vaccine
Abbreviations used : AD, CI, EASI, EASI-50, EASI-75, IGA, IL, IQR, MPSV4, SBA, TCI, TCS, Tdap, TEAE
Plan
| Funding sources: Sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Medical writing and editorial assistance were funded by Sanofi Genzyme and Regeneron Pharmaceuticals Inc. |
|
| Dr Evans is a previous employee of Regeneron Pharmaceuticals Inc. |
|
| Conflicts of interest: Dr Blauvelt has served as an investigator and consultant for AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira Inc, Eli Lilly and Co, Genentech/Roche, GlaxoSmithKline, Janssen, Leo Pharma, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron Pharmaceuticals Inc, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant, and Vidac and as a paid speaker for Eli Lilly and Co, Janssen, Regeneron Pharmaceuticals Inc, and Sanofi Genzyme. Dr Simpson has received grants or research support from Anacor Pharma, Eli Lilly and Co, GlaxoSmithKline, MedImmune, Novartis, Regeneron Pharmaceuticals Inc, Roivant Sciences, Tioga Pharmaceuticals Inc, and Vanda Pharmaceuticals Inc and has served as a consultant for AbbVie, Anacor Pharma, Celgene, Dermira Inc, Eli Lilly and Co, Galderma, Genentech, GlaxoSmithKline, LEO Pharmaceutical Inc, Menlo Therapeutics, Pfizer Inc, Regeneron Pharmaceuticals Inc, Sanofi Genzyme, and Valeant Pharmaceutical Co. Dr Tyring has served as an investigator for Regeneron Pharmaceuticals Inc. Drs Purcell, Shumel, Petro, Akinlade, Gadkari, and Graham are employees and shareholders of Regeneron Pharmaceuticals Inc. Drs Eckert and Pirozzi are employees of Sanofi and may hold stock or stock options in the company. Dr Evans was an employee of Regeneron Pharmaceuticals Inc at the time of the study and a shareholder of Regeneron Pharmaceuticals Inc. |
|
| Previously presented: These data were presented at the 35th Annual Congress of the European Academy of Allergy and Clinical Immunology in Vienna, Austria, on June 11-15, 2016. |
|
| Reprints not available from the authors. |
Vol 80 - N° 1
P. 158 - janvier 2019 Retour au numéro
Article précédent
- Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria
- Brian R. Gastman, Pedram Gerami, Sarah J. Kurley, Robert W. Cook, Sancy Leachman, John T. Vetto
- A novel topical minocycline foam for the treatment of moderate-to-severe acne vulgaris: Results of 2 randomized, double-blind, phase 3 studies
- Linda Stein Gold, Sunil Dhawan, Jonathan Weiss, Zoe Diana Draelos, Herman Ellman, Iain A. Stuart
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?